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Biomedical subjects

Peter Hellstern

Publications and source records attributed to Peter Hellstern.

15 recordsLinked to original sources
PubMed2005

The impact of cardiac ischemia and reperfusion on markers of activated haemostasis and fibrinolysis during cardiopulmonary bypass: comparison of plasma levels in arterial and coronary venous blood.

INTRODUCTION: Activation of coagulation and fibrinolysis is common among patients undergoing cardiopulmonary bypass (CPB) surgery. Little is known, however, about the impact of myocardial ischemia and reperfusion on coagulation activation and fibrinolysis in this clinical setting. STUDY DESIGN AND METHODS: We determined the levels of coagulation activation and fibrinolysis markers (CAFM) in 19 patients with severe coronary heart disease (CHD) during CPB surgery. FXIIa, tissue factor (TF), FVIIa, tissue plasminogen activator/plasminogen activator inhibitor-1 complexes (tPA/PAI-1), prothrombin fragments 1+2 (F1+2), D-dimers (DD) and plasmin-plasmin inhibitor complexes (PPI) were measured at baseline, prior to and after cardioplegic myocardial ischemia. Simultaneous blood samples were drawn from the aorta and the coronary sinus to evaluate arteriovenous CAFM plasma level gradients. RESULTS: Myocardial ischemia induced significant increases in gradients of FXIIa and F1+2 levels across the coronary circulation without influencing systemic levels of these markers significantly. Systemic levels of FXIIa, tPA/PAI-1, F1+2, DD and PPI increased significantly during CPB operation. There was a significant linear correlation between FXIIa, FVIIa, F1+2, DD and PPI. CONCLUSIONS: Myocardial ischemia induces contact activation and thrombin generation rather than release of tPA and might thus contribute to postoperative thromboembolic complications. Surgery itself and CPB cause activation of coagulation and fibrinolysis as already described. A significant association between FXIIa, FVIIa, F1+2, DD and PPI suggests a relationship between contact activation, thrombin generation, fibrin formation and fibrinolysis.

Aged↗
PubMed2005

The quality of plasma collected by automated apheresis and of recovered plasma from leukodepleted whole blood.

BACKGROUND: There exists a current lack of information about the composition of the different types of plasma. No direct comparisons between apheresis plasma (AP) and recovered plasma (RP) derived from in-line-filtered whole blood (WB) have been published to date. STUDY DESIGN AND METHODS: Sixty AP units, 100 RP units from in-line-filtered WB held for 3 hours at 20 degrees C between donation and freezing, and an additional 100 RP units held for 15 hours at 20 degrees C before freezing were analyzed for coagulation factors and inhibitors, total protein, immunoglobulin G (IgG), and hemostasis and proteolysis activation markers. The influence of twice freezing and thawing on clotting factors V, VIII, and XI was also examined. RESULTS: AP contains substantially greater activities of factor (F) V, FVIII, F IX, and FXI than RP frozen within 3 hours after WB donation. Prolonged holding of RP at 20 degrees C for more than 15 hours caused an additional reduction in FVIII, FXI, and protein S activities. Significantly greater levels of prothrombin fragments 1 and 2, platelet factor 4, and neutrophil elastase were found in RP compared with AP. IgG was lower in AP compared with RP. Twice freezing and thawing caused a marked drop in FV, FVIII, and FXI activity. CONCLUSION: Higher FVIII and F IX potencies in AP compared with RP can be expected to result in greater yields when used for purification of these clotting factors. AP is presumably more efficient than RP for treating coagulopathies. RP, however, may contain higher IgG levels than AP.

Adult↗
PubMed2005

Relationship between factor XIII activity, fibrinogen, haemostasis screening tests and postoperative bleeding in cardiopulmonary bypass surgery.

We investigated the relationship between factor XIII, fibrinogen, blood coagulation screening tests and postoperative bleeding in 98 patients undergoing cardiopulmonary bypass (CPB) surgery. All patients received aprotinin. Blood samples were collected preoperatively (T1),after termination of CPB (T2),12 h (T3) and 24 h (T4) after surgery to determine FXIII activity, fibrinogen, platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT) and D-dimers (DD). Laboratory results were correlated with the chest tube drainage 24 h after surgery and compared between patients with 24-hour chest tube drain volumes in the lower (Group 1) with those in the upper tertile (Group 3). Median FXIII and fibrinogen levels dropped by 33.9% and 34.2%, respectively, during CPB. No association between FXIII activity and the extent of postoperative bleeding was found. However, chest tube bleeding was significantly correlated with preoperative and postoperative fibrinogen. This was confirmed by comparing Groups 1 and 3. Group 3 patients had significantly lower fibrinogen levels than Group 1 at T1 - T4, although most fibrinogen values were within or above the reference range (medians, g/l: 3.5 vs. 4.0, p = 0.043 at T1; 2.3 vs. 2.7, p = 0.015 at T2; 2.9 vs. 3.3, p = 0.008 at T3; 4.2 vs. 5.2, p = 0.002 at T4). There was also a significant relationship of platelet count, PT and APTT, as measured after CPB (T2), with postoperative chest tube drainage. In conclusion, plasma FXIII activity does not influence postoperative bleeding in patients undergoing CPB surgery. There is however an inverse association between preoperative or postoperative plasma fibrinogen levels and postoperative bleeding. These findings indicate a modulation of postoperative bleeding by fibrinogen levels.

Adult↗
PubMed2004

Solvent/detergent-treated plasma: composition, efficacy, and safety.

PURPOSE OF REVIEW: Recent reports on adverse events associated with solvent/detergent-treated plasma have raised concerns about the efficacy and safety of this type of therapeutic plasma. Comparisons of various brands of solvent/detergent-treated plasma have revealed substantial differences in their composition. RECENT FINDINGS: Retrospective analyses and case reports suggest an association between the low protein S activity levels found in solvent/detergent-treated plasma and venous thromboembolism when solvent/detergent-treated plasma is given for thrombotic thrombocytopenic purpura or transfused massively during liver transplantation surgery. Augmented bleeding caused by hyperfibrinolysis, possibly caused by the low plasmin inhibitor (also termed alpha2-antiplasmin) activity of solvent/detergent-treated plasma, has also been a matter of concern. The efficacy and safety of various types of solvent/detergent-treated plasma have been studied intensively for all indications for therapeutic plasma by at least five prospective trials, four observational studies, and post-licensure monitoring. A review of the literature shows that the clinical significance of transient protein S and plasmin inhibitor deficiency has been considerably overstated, even when such deficiency might be aggravated by the administration of large amounts of solvent/detergent-treated plasma. However, different brands of solvent/detergent-treated plasma differ substantially with respect to their composition and hemostatic balance. It cannot be completely excluded that the very low citrate and protein S concentrations versus higher clotting factor concentrations found in a given brand of solvent/detergent-treated plasma could contribute to coagulation activation in the settings of thrombotic thrombocytopenic purpura and liver transplantation. SUMMARY: Future research should seek to optimize the composition of solvent/detergent-treated plasma. Prospective trials and prospective hemovigilance studies are required to determine the rate of adverse events occurring after treatment with solvent/detergent-treated plasma and other types of therapeutic plasma.

Blood Component Transfusion↗
PubMed2003

Laboratory monitoring of heparin and the combination of heparin and the platelet glycoprotein IIb/IIIa receptor antibody fragment abciximab (c7E3) in patients undergoing percutaneous transluminal coronary angioplasty (PTCA).

BACKGROUND: Previous studies in patients undergoing percutaneous transluminal coronary angioplasty (PTCA) have restricted laboratory monitoring to the activated clotting time (ACT). It remains unknown whether the ACT-prolonging effect of abciximab is clinically equivalent to a comparable degree of anti-coagulation by heparin. PATIENTS AND METHODS: 30 patients undergoing PTCA received 100 IU of heparin/kg body weight. Another 30 patients received an initial bolus of 70 IU of heparin/kg + abciximab. We determined ACT, laboratory and onsite activated partial thromboplastin time (APTT) and plasma heparin levels. RESULTS: Despite markedly different preintervention heparin dosing, the ACTs were not significantly different between groups. After termination of PTCA, the median ACTs of both study groups were nearly equivalent (267 vs. 272 s; p = 0.79). The median ACT-prolonging effect of abciximab could be equated with 0.68 IU/ml heparin. Both APTT assays were not suitable for monitoring the anticoagulant effects during PTCA due to their high sensitivity. By contrast, the plasma heparin levels clearly reflected the different heparin doses. The weak correlation (r = 0.23) between ACTs and heparin levels in patients receiving heparin + abciximab was due to excessively prolonged ACTs in six patients (540-1,245 s). These data could be attributed to an unusually high response to abciximab. By contrast, the ACT was a reliable measure of the anticoagulant effect of heparin in patients receiving exclusively heparin. CONCLUSIONS: ACT reflects both heparin and abciximab therapy, whereas heparin levels reflect only heparin dose. The APTT assays were not suitable for monitoring the anticoagulant effects during PTCA.

Abciximab↗
PubMed2003

Screening for multiple hereditary hypercoagulability factors using the amplification refractory mutation system.

Many hereditary factors have been implicated in the development of arterial and/or venous thromboembolic diseases. A number of these risk factors can be identified by the amplification refractory mutation system (ARMS). However, the underlying technical conditions for performing ARMS are highly variable, and depend on which risk factors are being analyzed. We have now developed a novel ARMS-based system to simultaneously screen for multiple hypercoagulability factors under identical PCR conditions. This can greatly simplify the process of screening for hereditary hypercoagulability.

Base Sequence↗
PubMed2003

The impact of intensive serial plasmapheresis and iron supplementation on iron metabolism and Hb concentration in menstruating women: a prospective randomized placebo-controlled double-blind study.

BACKGROUND: Iron (Fe) depletion is common among regular whole-blood donors, but can be prevented through regular oral Fe supplementation. Little is known, however, about the Fe metabolism of donors undergoing intensive plasmapheresis. These donors lose considerable amounts of blood drawn for laboratory analyses and remaining in the disposable plastic sets. STUDY DESIGN AND METHODS: Menstruating women were enrolled in a prospective placebo- controlled double-blind study. One hundred women were randomly allocated to receive either 100 mg of elemental Fe per day or placebo over 24 weeks and asked to donate plasma at 1-week intervals. Hb was determined before each plasmapheresis. Ferritin, transferrin, and Fe concentration and reticulocyte count were measured every 4 weeks. RESULTS: Thirty donors in the placebo group and 29 receiving Fe completed the study. The total mean blood loss was 526 mL in the placebo group and 546 mL in the Fe arm (p=0.271). The number of donations with Hb values lower than 12.5 g per dL requiring prolongation of the time interval until the next plasmapheresis was significantly greater in the placebo arm. In the placebo group (n=30), ferritin levels began to decline significantly 4 weeks after entry. When the study was completed, Hb concentration and reticulocyte count also were found to be significantly lower in the placebo group than in the Fe study arm (p=0.028 and p=0.036, respectively). Hb, ferritin, and transferrin levels and reticulocyte counts did not change significantly in the Fe group during the observation period. CONCLUSION: Menstruating women undergoing regular plasmapheresis at short intervals are prone to develop Fe depletion. This can be prevented by regular Fe intake. Laboratory analyses in product plasma instead of serum gained from whole-blood samples could be an alternative to reduce blood loss.

Adult↗
PubMed2002

Manufacture and composition of fresh frozen plasma and virus-inactivated therapeutic plasma preparations: correlation between composition and therapeutic efficacy.

The clinical efficacy of the therapeutic plasma used in the treatment of congenital and acquired severe coagulopathy depends on the potency of clotting factor and inhibitor activities. The composition of plasma strongly depends on the conditions under which it is produced. A low citrate anticoagulant-to-blood ratio, short intervals between donation and plasma separation and rapid freezing markedly improve the preservation of unstable coagulation factors. The influence of different leukocyte reduction filters on plasma quality still requires clarification. Recent trials on long-term storage conditions suggest that keeping plasma at -30 degrees C or colder over a period of 24-36 months prevents substantial decrease in clotting factor activities including factor VIII (FVIII). Three types of therapeutic plasma are currently available. Quarantine-stored fresh frozen plasma (FFP) contains physiological activities of therapeutically relevant plasma proteins, but carries a risk of transmitting blood-borne viruses that cannot be detected by human immunodeficiency virus (HIV) and hepatitis B and C screening. In contrast, solvent/detergent-treated plasma (SDP) and methylene blue/light-treated plasma (MBP) is virtually free of HIV and hepatitis C virus (HCV) subtypes. Virus inactivation procedures can have the consequence of reducing several clotting factors and inhibitors in SDP and MBP to varying degrees. However, pooling of plasma units before solvent/detergent (SD) treatment results in well-standardized protein levels of SDP. At least five prospective trials and four observational studies covering different clinical settings suggest that SDP and FFP do not substantially differ in their clinical efficacy or in their tolerance. By way of contrast, there is a lack of data about the clinical efficacy and tolerance of MBP compared to FFP.

Blood Coagulation Factors↗
PubMed2002

Indications for plasma in massive transfusion.

The initial aim in massive transfusion (MT) is to supply crystalloids, colloids, and plasma-poor red cell concentrates (RCCs) to maintain normovolemia and oxygen supply. This frequently leads to dilution coagulopathy, which is frequently aggravated and accelerated by hypothermia, acidosis, shock-induced impairment of liver function and disseminated intravascular coagulation (DIC), and increased consumption of clotting factors and platelets at extensive wound sites. Disorders of hemostasis deteriorate the prognosis of massively transfused patients dramatically. Therefore, the second therapeutic objective is the timely administration of plasma and platelet concentrates as required to halt the microvascular bleeding (MVB) induced by impaired hemostasis. Close laboratory monitoring, to include as a minimum platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen, is essential to identify hemostatic disorders requiring therapeutic intervention. Coagulopathy promoting microvascular bleeding can be assumed when PT or APTT values exceed 1.5 times mean controls and/or when fibrinogen levels fall below 1.0 g/l. Repeated rapid infusion of 10-15 ml plasma per kg of body weight will be required to raise clotting factor levels significantly and to achieve adequate hemostasis. The turnaround time for obtaining laboratory results and for readying plasma for transfusion must be taken into particular consideration in cases of rapid blood loss.

Blood Component Transfusion↗
PubMed2002

Therapeutic plasma exchange and plasma infusion in thrombotic microvascular syndromes.

Plasma exchange (PE) is the most important treatment in thrombotic microangiopathies (TMAs) mainly encompassing thrombotic thrombocytopenic purpura (TTP) and adult hemolytic syndrome (HUS). This therapeutic measure has substantially improved clinical outcome. One plasma volume corresponding to 40 ml/kg of body weight is exchanged daily until the platelet count is above 150 x 10(9)/l or 100 x 10(9)/l and continues to rise or remains constantly after cessation of treatment. Exacerbations and late recurrences demand reapplication of daily PE. Twice daily PEs are initiated if the response to initial treatment is poor. The importance of additional or alternate measures including glucocorticoids, antiplatelet agents, splenectomy, intravenous immunoglobulins, protein A columns, vincristine, cyclosporine, and cyclophosphamide is uncertain. Whether cryosupernatant plasma (CSP) or solvent/detergent-treated (SDP) plasma is superior to standard fresh frozen plasma (FFP) remains to be determined. Methylene blue-treated plasma (MBP) seems to be less effective than standard FFP.

Hemolytic-Uremic Syndrome↗
PubMed2002

Practical guidelines for the clinical use of plasma.

Despite differences in the composition of fresh frozen plasma (FFP) and solvent/detergent-treated plasma, prospective controlled clinical trials have not revealed any significant difference in clinical efficacy and tolerance between the two types of plasma. Evidence of the clinical efficacy of plasma is mainly based on expert opinion, case reports, and on controlled and uncontrolled observational studies. The application of plasma without laboratory analysis to verify the coagulopathy is normally not justified. With the exception of emergency situations when timely clotting assay results are not available, the administration of plasma in coagulopathy must be verified both clinically and by laboratory analysis before plasma is administered. The rapid infusion of at least 10 ml plasma/kg of body weight is required to increase the respective plasma protein levels significantly. Based on the present state of knowledge, plasma is indicated for complex coagulopathy associated with manifest or imminent bleeding in massive transfusion, disseminated intravascular coagulation, and liver disease. Therapeutic plasma exchange with 40 ml plasma/kg of body weight is the treatment of first choice in acute thrombotic-thrombocytopenic purpura-adult hemolytic uremic syndrome (TTP-HUS). A rare indication is the treatment or prevention of bleeding in congenital factor V or factor XI deficiency, plasma exchange in neonates with severe hemolysis or hyperbilirubinemia, and filling of the oxygenator in extracorporeal membrane oxygenation (ECMO) in neonates. Prothrombin complex concentrates should be preferred to plasma for the reversal of oral anticoagulation in emergency situations, since controlled studies have shown a minor efficacy of plasma. Side effects resulting from the administration of plasma are rare but have to be considered.

Blood Coagulation Disorders↗
PubMed2002

Topical application of aprotinin in cardiac surgery.

The aim of our study was to compare a systemic and a local aprotinin application in patients during coronary artery bypass graft (CABG) surgery. The advantage of a topical aprotinin application is seen in the fact that this may not lead to systemic side effects. A prospective, randomized study comprising 97 patients was conducted. A dose of 5 x 10(6) KIU aprotinin was given systemically to 49 patients and four doses of 1.25 x 10(6) KIU aprotinin were applied topically to 48 patients by spraying the substance on the target area (A. mammaria interna region and pericardium). We determined markers for the inflammatory response, coagulation system, standard haematological markers and postoperative complications. Exclusion criteria were defined as surgical bleeding, redo operations, neurological, haematological, liver and kidney disorders. Sex, age, perfusion times, mortality, renal failure and strokes were identical in both groups. Biochemical markers and clinical outcome demonstrated no significant differences between the systemic and local applications. Interleukin 6 and elastase were tendentially higher (p = 0.1) in the local group, but with a high standard deviation in each patient. Our results suggest that there is no difference between the perioperative application of 5 x 10(6) KIU systemically given aprotinin and 1.25 x 10(6) KIU locally applied aprotinin.

Administration, Topical↗
PubMedDate not supplied

Recurrent pregnancy loss and its relation to FV Leiden, FII G20210A and polymorphisms of plasminogen activator and plasminogen activator inhibitor.

Thrombophilic disorders and hypofibrinolysis were demonstrated to be risk factors in a majority of women with recurrent pregnancy loss (RPL) and infertility. We investigated the association of FV G1691A mutation, F II G20210A gene polymorphism (PM), 4G/5G PAI-1 and Alu I/D tPA PM in 32 women with infertility and 49 women with at least 2 unexplained early abortions. FV Leiden mutation was significantly more common in women with RPL (10%, p = 0.02) and infertility (19%, p = 0.0005) compared with controls (2%). PAI-1 4G PM and t-PA Alu I PM, alone or in combination, were not associated with RPL or infertility. 9/49 women with RPL showed coagulation disorders with heterozygous FV Leiden mutation (5), FXII (1), protein C (1) or protein S (2) deficiency. However, due to the small number of patients studied, no definite conclusion can be drawn.

Abortion, Habitual↗